Project Summary/Abstract Seasonal malaria chemoprevention (SMC), is a prophylactic antimalarial regimen of sulfadoxine- pyrimethamine (SP) and amodiaquine (AQ) recommended by the World Health Organization (WHO) for pre- venting malaria episodes in children under 5 years of age in specific, highly seasonal, transmission settings. In 2012, the WHO called on all countries in the Sahel sub-region of Africa to implement SMC. The WHO reports that SMC is 75% effective in preventing all malaria episodes and 75% of severe malaria episodes when im- plemented according to its guidelines. From 2013-2016, the West African International Centers of Excellence for Malaria Research (ICEMR) carried out a cohort study including 1,814 subjects in a remote village in Dangassa, Mali. Peak malaria incidence reductions following SMC coverage in children less than 5 years of age were observed in 2015 at 38%, falling far short of the 75% protective efficacy suggested by the WHO. These estimates call into question the effectiveness of SMC implementation or the efficacy of the therapy itself in high malaria transmission in Mali like Dangassa. The purpose of the proposed study is two-fold. First, cross- sectional and cohort studies are used to establish levels of SMC coverage and implementation practices to as- sess effectiveness of SMC. Second, if results suggest operational, implementation, SP or AQ resistance and SMC coverage practices are acceptable, a randomized control trial will be conducted to measure the effective- ness of extending SMC to children up to 10 years of age. Alternatively, if operational and implementation strategies are found to be functioning poorly and drug resistance is found to be at acceptable levels suggesting the potential for efficacy of well implemented SMC, a randomized control trial will be used to assess the effec- tiveness of different delivery systems to achieve the intended effect by improving coverage. The findings from years 1 and 2 implementation studies will serve as the go (conduct high quality efficacy study) versus no-go (conduct further intervention effectiveness studies around operations and implementation strategies) criteria for years 3-5.